Definition/General
Introduction:
Phyllodes tumors are rare fibroepithelial tumors of the breast that are classified as benign, borderline, or malignant based on histological features
Malignant phyllodes tumors account for about 25% of all phyllodes tumors and have the potential for local and distant recurrence.
Origin:
They arise from the intralobular stroma of the breast
They are composed of a benign epithelial component and a malignant stromal component.
Classification:
The classification into benign, borderline, and malignant is based on a combination of features: stromal cellularity, stromal atypia, mitotic activity, stromal overgrowth, and the nature of the tumor borders (pushing vs
infiltrative).
Epidemiology:
Phyllodes tumors are most common in women in their 40s
Malignant phyllodes tumors tend to occur at a slightly older age
They are rare, accounting for less than 1% of all breast tumors.
Clinical Features
Presentation:
Typically presents as a large, rapidly growing, palpable breast mass
The mass is usually firm and mobile
Skin changes like ulceration can occur with very large tumors.
Symptoms:
A painless, large breast lump is the most common symptom
The rapid growth can cause a sensation of pressure or discomfort.
Risk Factors:
The exact cause is unknown
They are not strongly associated with the common risk factors for breast carcinoma
A history of a benign phyllodes tumor or fibroadenoma may be present.
Screening:
They are usually diagnosed after a palpable mass is investigated
On mammography, they appear as large, well-circumscribed, lobulated masses
Ultrasound shows a solid mass, sometimes with cystic spaces.
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Gross Description
Appearance:
A large, well-circumscribed, lobulated mass
The cut surface has a characteristic leaf-like (phyllodes) appearance with whorled, fleshy, gray-white tissue and cystic spaces.
Characteristics:
Malignant tumors are often larger (>5 cm) and may show areas of necrosis and hemorrhage
The borders can be infiltrative.
Size Location:
Can occur anywhere in the breast
Size is highly variable, but malignant tumors are typically large.
Multifocality:
Multifocality is rare.
Microscopic Description
Histological Features:
Biphasic tumor with a benign epithelial component and a malignant stromal component
The stroma is hypercellular and shows marked atypia, high mitotic activity (>10 per 10 high power fields), and stromal overgrowth (absence of epithelium in at least one low power field).
Cellular Characteristics:
The stromal cells are spindle-shaped and pleomorphic with hyperchromatic nuclei and frequent, often atypical, mitotic figures
The epithelial component consists of benign ductal structures.
Architectural Patterns:
The characteristic leaf-like architecture is formed by the proliferation of the stroma into the cystic spaces lined by epithelium
Infiltrative borders are a key feature of malignancy.
Grading Criteria:
The diagnosis of malignant phyllodes tumor is based on the combination of marked stromal hypercellularity, marked stromal atypia, high mitotic rate, stromal overgrowth, and infiltrative margins.
Immunohistochemistry
Positive Markers:
The stromal cells are positive for vimentin and CD34
They may show variable positivity for smooth muscle actin and desmin
The epithelial component is positive for cytokeratins.
Negative Markers:
The stromal cells are negative for cytokeratins
Hormone receptors (ER, PR) are usually negative in the stroma but can be positive in the epithelial component
HER2 is negative.
Diagnostic Utility:
IHC helps in differentiating from other spindle cell lesions of the breast
CD34 can be useful
Ki-67 shows a high proliferation index in the stromal cells.
Molecular Subtypes:
Not applicable in the same way as for breast carcinomas
The focus is on the stromal component.
Molecular/Genetic
Genetic Mutations:
Mutations in MED12 and TERT promoter are common
Malignant phyllodes tumors show complex karyotypes with numerous chromosomal gains and losses
TP53 mutations can be seen.
Molecular Markers:
Overexpression of genes involved in cell cycle progression and proliferation, such as CDK4 and MDM2.
Prognostic Significance:
Malignant phyllodes tumors have a high risk of local recurrence (around 20-30%) and a risk of distant metastasis (around 20-25%), most commonly to the lungs
The prognosis is significantly worse than for benign or borderline tumors.
Therapeutic Targets:
Treatment is primarily surgical, with wide local excision or mastectomy to achieve clear margins
The role of adjuvant chemotherapy and radiation is not well-established and is considered on a case-by-case basis.
Differential Diagnosis
Similar Entities:
Fibroadenoma (cellular)
Metaplastic carcinoma
Primary breast sarcoma
Benign or borderline phyllodes tumor.
Distinguishing Features:
Cellular fibroadenomas lack the marked atypia, high mitotic rate, and stromal overgrowth of malignant phyllodes
Metaplastic carcinomas have a malignant epithelial component (positive for cytokeratins)
Primary breast sarcomas lack an epithelial component
Distinguishing from borderline phyllodes can be difficult and depends on the degree of the histological features.
Diagnostic Challenges:
The distinction between borderline and malignant phyllodes tumors can be subjective and requires careful evaluation of all histological parameters
Core biopsy may not be representative of the entire tumor, leading to under-grading.
Rare Variants:
Malignant phyllodes tumors can show heterologous stromal differentiation (e.g., liposarcoma, chondrosarcoma, osteosarcoma), which should be noted in the report.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type], measuring [size] cm in greatest dimension
Diagnosis
[diagnosis name]
Classification
Classification: [classification system] [grade/type]
Histological Features
Shows [architectural pattern] with [nuclear features] and [mitotic activity]
Size and Extent
Size: [X] cm, extent: [local/regional/metastatic]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: [marker]: [result]
Molecular: [test]: [result]
[other study]: [result]
Final Diagnosis
Final diagnosis: [complete diagnosis]